tbuckley/cabot-search huggingface dataset:
A comprehensive analysis of clinical characterization in 149 Chinese patients with Lynch syndrome.
Authors: Junqiong Lin, Rongrong Kong, Tiantian Han, Didi Guo, Yuwei Dong, Siqi Chen, Yang Chen, Wanglong Deng, Ran Ding, Fanfeng Bu, Mengjuan Wang
Journal: Journal of Clinical Oncology (2023)

10606 Background: Lynch syndrome (LS) caused by germline pathogenic variants (PVs) in mismatch repair (MMR) genes, which increased risk of malignancy in different organs. LS-related tumors included colorectal, endometrial, gastric, ovarian, pancreas, urinary system, biliary tract, central nervous system, skin and small intestinal carcinomas (CRC, EC, GC, OC, PC, UST, BTC, CNST, SC, SIC). As sequencing technology becomes more economical and widespread, more MMR PVs were detected in LS-unrelated tumors. The aim of this study was to explore the clinical characterization in Chinese real-world LS solid tumor. Methods: We applied next-generation sequencing (NGS) screening to detect the germline mutation in MMR (include MLH1, MSH2, MSH6, PMS2), tumor mutation burden (TMB) and microsatellite instability (MSI) in Chinese solid tumor patients (pts). In the cohort, lung cancer (LC) was the most common cancer type, followed by CNST, CRC, hepatic carcinoma (HC). Results: 149 LS pts were observed in our cohort, among which 81.2% (121/149) carried LS-related tumors (44 CRC, 47 CNST, 9 EC, 9 BTC, 4 UST, 3 OC, 2 GC, 2 SC, 1 SIC), 18.8% (28/149) carried with LS-unrelated tumors(18 LC, 5 HC, 3 sarcoma, 1 ampullary carcinoma, 1 peritoneal cancer), and the age showed no significant difference between LS-related tumors and LS-unrelated tumors (average age: 48 vs 53, p=0.08). The distribution of MMR PVs were as follows: MLH1 (37, 24.8%), MSH2 (46, 30.9%), MSH6 (34, 22.8%), PMS2 (32, 21.5% ), and comparative analysis showed that LS-related tumors tended to carry MLH1 and MSH2 PVs (60.3%, 73/121), while LS-unrelated tumors tended to carry MSH6 and PMS2 PVs (67.9%, 19/28) ( p&lt;0.05). 46.3% LS pts had MSI-H, concentrated in MLH1 or MSH2 PVs carriers. MSI-H showed a higher detection rate in LS-related tumors other than LS-unrelated tumors(56.1% vs 3.6%, p&lt;0.005). Among LS-related tumors, the top 3 prevalence of MSI-H were CRC (93.2%, 41/44), BTC (55.6%, 5/9) and EC (44.4%, 4/9), which were lower in CNST (31.9%, 15/47). In addition, we found that the rate of TMB-H in LS-related tumors was also higher than LS-unrelated tumors ( p&lt;0.001). Conclusions: In our dates, 18.8%(28/149) LS pts carried with LS-unrelated tumors, which emphasized the importance of germline genetic assessment for LS in pan-cancer. In addition, MSI-H, TMB-H and MMR PVs distributions were significantly different in LS-related tumors and LS-unrelated tumors. The differences about LS clinical characterization associated with MMR genes require further study.
Effects of different immune microenvironment characteristics on effect of immune checkpoint inhibitors in solid tumors with <i>TGFBR2</i> mutation.
Authors: Rongrong Yao
Journal: Journal of Clinical Oncology (2023)

e21027 Background: TGFBR2 is a member of the TGF-β receptor family, the protein encoded by it was involved in the regulation of cell proliferation, apoptosis, differentiation and other biological processes. TGFBR2 mutation can affect the occurrence of tumors. previous research showed that the TGF-β signaling pathway suppresses the tumor immune response, so TGFBR2 mutations may lead to tumor resistance to immunotherapy. However, effect of TGFBR2 mutations on ICIs and its correlation with immune microenvironment are rarely explored. Methods: NGS data from an independent cohort (the MSKCC study cohort) of 1661 patients and Chinese clinical dataset (panel on 733-gene) of 35337 patients with pan-cancer to explore the association between PTCH1 mutations and immune biomarkers. TMB was defined as total number of somatic non-synonymous mutations in coding region. MSI was evaluated by NGS of 500 known MSI loci. PD-L1 expression was evaluated using immunohistochemistry (Dako 22C3). Patients from three independent cohorts (OAK, POPLAR and MSKCC study cohort) and were used to analyze the correlation between PTCH1 mutations and the efficacy of immune checkpoint blockade immunotherapies (ICIs). Estimation of immune filtration cells scores were conducted via TIMER2.0 (http://timer.cistrome.org/). Results: In Chinese cohort, there were 831 (4.32%) patients harboured TGFBR2 mutation ( TGFBR2 mut ), in which the most number patients with TGFBR2 mut were gastric carcinoma (10.53%), followed by colorectal (8.63%) and NSCLC (2.98%). Same as the MSKCC cohort (2.77%). For the TMB, both Chinese (median, 28.64 Muts/Mb vs 8.39 Muts/Mb, P ＜0.001) and MSKCC (median, 28.53 Muts/Mb vs 6.89 Muts/Mb, P = 0.030) cohort were associated with higher TMB than the wild-type. Supplemental analysis of MSI in the Chinese cohort showed significant differences between the TGFBR2 mut and TGFBR2 wt groups (P ＜0.001), but not on PD-L1 levels (P = 0.50). In terms of prognostic effect with ICIs therapy, TGFBR2 mut were significantly associated with the overall survival (OS) of NSCLC (median, 2 months vs 11 months; HR = 3.46; 95% CI, 1.63-7.35; P ＜0.001) in OAK and POPLAR cohort, same as MSKCC cohort (median, 3 months vs 10 months; HR = 2.21; 95% CI, 1.04-4.71; P = 0.034). Interestingly, In the MSKCC cohort, opposite with NSCLC, majority tumors with TGFBR2 mut had a longer survival value, showing a trend toward longer survival. Exploring the correlation between TGFBR2 and immune microenvironment. The results showed NK cell (P = 0.042) and CD4+ T cell (P = 0.036) infiltration were significantly negatively correlated in NSCLC. However, other solid tumors such as colorectal and melanoma are opposite. Conclusions: The results showed that the TGFBR2 had a high correlation in solid tumors with TMB and MSI. The TGFBR2 might a potential biomarker for ICIs therapy in NSCLC, and the immune microenvironment may be a factor affecting of it.
Survival for patients of stage III non-small cell lung cancer after radiotherapy in different periods.
Authors: Zhuofan Wang, Qi Liu, Yuxiang Wang, Zhan Qi, Zhimen Zhang, Jian Shi, Xinyuan Chen, Jian Zhang, Yuan Wang, Zhongfei Jia, Meng Song, Yan Zhao
Journal: Journal of Clinical Oncology (2023)

e20611 Background: Concurrent chemoradiotherapy (CCRT) is the main treatment for patients of unresectable stage Ⅲ non-small cell lung cancer (NSCLC).To retrospectively analyze prognosis and its related factors for patients of unresectable stage III NSCLC after radiotherapy in different periods. Methods: From 2000 to 2010 and from 2015 to 2019, patients of stage III NSCLC which received radiotherapy in the Fourth Hospital of Hebei Medical University were enrolled. Statistical analysis was used with the SPSS 21.0 software.The Kaplan-Meier method, log-rank test and Cox model were used for survival analysis, univariate analysis, and multivariate analysis, respectively. Results: A total of 808 patients of stage III NSCLC were enrolled. There were 674 males and 134 females. The median age was 63 years old( 29-86 years old ) . Radiotherapy (RT) were performed in 474 patients between 2000 to 2010 and in 334 patients between 2015 to 2019. There were 240 cases received with RT alone, 449 cases with sequential chemoradiotherapy (Seq-CRT) and 119 cases with CCRT. 55 were treated with 3-dimensional radiotherapy (2DRT) plus 3-dimensional conformal radiotherapy (3DCRT)，386 with 3DCRT，and 367 with intensity-modulated radiotherapy（IMRT)， respectively. The median doses was 60 Gy (range 36-77Gy). The median overall survival (OS) was 21.0 months (19.4-22.6 months), and the 1-, 3- and 5-year OS rates were 69.8%, 30.7% and 21.3%, respectively. Under univariate analysis, gender, age, radiotherapy technology，period of treatment and whether combined chemotherapy were significantly associated with OS ( P&lt; 0.05). The median OS was 18.0 months in group of 2000-2010 and 26.1 months in group of 2015-2019, respectively. The median OS for groups of2DRT+3DCRT, 3DCRT and IMRT were 10.0, 21.0, 23.4 months, respectively. The median OS for RT alone, Seq-CRT and CCRT was 17.0, 21.0, 30.3 months, respectively. Under multivariate analysis, sex, age, times of RT and combined chemotherapy were independent prognostic factors for OS ( P&lt; 0.05). Conclusions: From 2DRT to 3DCRT or IMRT, the OS in patients of stage Ⅲ NSCLC was gradually increased; the OS was more higher in patients treated between 2015-2019 also. In addition, the OS was significantly longer in patients with CCRT than with Seq-CRT or RT alone.
Breast cancer staging for patients with “low risk” disease: Are they all the same?
Authors: Jennifer Kay Plichta, Samantha M. Thomas, Sydney Record, Astrid Botty van den Bruele, Akiko Chiba, Gayle DiLalla, Maggie DiNome, Laura Horst Rosenberger, Hannah Woriax, Eun-Sil Shelley Hwang
Journal: Journal of Clinical Oncology (2023)

6584 Background: Studies have shown that a low (&lt;11) Oncotype DX recurrence score (RS) is associated with better survival outcomes. RS is currently included in the AJCC prognostic staging criteria. Not all patients with a low RS are downstaged. It has been suggested that a low RS should further downstage patients regardless of other disease factors. We explored survival outcomes for patients with a low RS to assess if additional patients should be downstaged. Methods: Using the National Cancer Database, female patients ages 18-75 with invasive unilateral pT1-3, pN0-1, M0 hormone receptor positive (ER+ and/or PR+), HER2- breast cancer and a RS &lt;11, diagnosed 2010-2018 were identified. Patients who received neoadjuvant treatment were excluded. Patients were grouped based on the AJCC 8 th edition prognostic stage (IA, IB, IIA, IIB, IIIA). Variables were summarized, and unadjusted overall survival (OS) was estimated using the Kaplan-Meier method. Cox proportional hazards models were used to estimate the association of stage with OS after adjustment for available covariates. Results: Of the 54,961 patients with a RS &lt;11, median follow-up was 57.7 months (95% CI 57.3-58.1), and median age was 61yo (IQR 52-67). Most tumors were grade 1 (37.6%) or 2 (56.9%) with ductal histology (75.3%). The median tumor size was 1.5 cm (IQR 1-2), and most were pN0 (83.3%). Although most patients with a RS &lt;11 were stage IA (94.2%), some had a higher stage assignment (5.1% stage IB, 0.6% IIA, 0.1% IIB, &lt;0.01% IIIA). Most patients (93.4%) received endocrine therapy (ET), and few (3%) received chemotherapy. Patients treated with chemotherapy more often had younger age, lobular histology, higher grade, larger tumor size, and/or pN+ disease (all p&lt;0.001). Unadjusted OS was reduced with higher stage (log-rank p&lt;0.001), and this remained true when limited to only those who received ET without chemotherapy (log-rank p&lt;0.001). After adjustment for relevant covariates including treatment, higher stage remained associated with worse OS [stage IA: ref; IB: HR 1.66 (95% CI 1.34-2.05); IIA: HR 2.29 (95% CI 1.44-3.65); IIB: HR 2.48 (95% CI 1.03-5.95); overall p&lt;0.001]. Conclusions: For patients with a low RS, survival outcomes vary with current AJCC prognostic disease stage, suggesting that not all patients with a RS &lt;11 should be downstaged based on RS alone. Anatomic and other non-genomic factors remain relevant when assessing prognosis. [Table: see text]
Geographical impact on prostate cancer genetic testing eligibility: A preliminary study from an academic cancer center.
Authors: Samantha Beck, Jonathan David Tward, Amanda Gammon, Samantha Greenberg
Journal: Journal of Clinical Oncology (2023)

10618 Background: Germline testing (GT) for prostate cancer (PCa) helps to determine treatment selection and other cancer risk, which guides screening recommendations. Patients with PCa that is high risk group by NCCN and greater stage should receive genetic counseling (GC) referral. There is limited data on differences in genetic services given the rurality of PCa patients. This study aims to determine the geographical distribution of PCa patients meeting GC referral and GT criteria. Methods: A retrospective analysis evaluated data from electronic medical records of PCa patients at an NCI-designated cancer research facility. Data was abstracted from new PCa patients seen in 2019 and 2021, years before and after the COVID-19 pandemic. Data includes demographic information, cancer staging, and pathology results. Regions of urbanicity, urban and non-urban (rural/frontier), were categorized through zip codes and defined by Utah Department of Health and Human Services. Criteria for GT followed NCCN guidelines (v.1.2023). Statistical methods for descriptive and comparative analysis done using Chisquare, Fisher’s exact, and Mann Whitney tests in R*Stats to compare 2019 and 2021 cohorts. Results: Out of 525 PCa patients' initial treatment at HCI in 2019 (n = 346) and 2021, (n = 179) 94% self-reported as White (p = 0.164) with a median age of 66 (p = 0.690) and 51% being employed (p = 0.396) at time of first treatment. Of these, 414 (79%) were from an urban area and 111 (21%) from a non-urban area (p = 0.883). The cohort was primarily from 2019 (66%), with 274 (79%) and 72 (21%) of the PCa patients living in urban and non-urban areas, respectively. In 2021 (34%), 140 (78%) and 39 (35%) patients were from urban and non-urban areas. Criteria for GT were met in 37% (n = 196) of PCa patients (p = 0.595). Regions were independently compared by race, age, employment, and year. No statistical difference across all variables was found (p &gt; 0.05). Geographical regions did not impact GT eligibility. Conclusions: This preliminary study shows that geographical region does not impact GT eligibility in PCa patients seen at HCI during 2019 and 2021. The years analyzed is a proxy for differences in aggressiveness by rurality. The results show 37% of the PCa patients met criteria for GT. No significant differences were identified by geographical region, race, age, employment, or the year of initial treatment. Further research is being conducted to determine if access to PCa GC uptake is impacted by geography and differing service delivery models after criteria for GT has been met.
Carcinoid tumor of the bronchus and lung: A nationwide cross-sectional study.
Authors: Esmirna Perez, Nehemias Guevara, Shellsea Portillo, Garry Francis-Morel
Journal: Journal of Clinical Oncology (2023)

e20645 Background: Carcinoid tumor of the lung is a rare neuroendocrine tumor (NET), little is known of the in-hospital characteristics of this tumor. This study aims to describe the characteristics of patients hospitalized with NET of the bronchus and lung. Methods: This is a retrospective descriptive study of patients with lung carcinoid tumors admitted to acute care from 2016 to 2020. Data is derived from the National Inpatient Sample (NIS). The patients were divided into two groups: malignant and benign carcinoid tumors of the bronchus and lung. Patients' characteristics were described, including demographics, hospital length of stay (Los), and total cost. Mortality and common comorbidities were included. Hypothesis testing for categorical variables were tested with Chi-Square. Continuous variables were tested with a Student t-test. Statistical significance was defined as a two-tailed P value of &lt; 0.05. Results: A total of 13,335 admissions were identified over a period of 5 years, but only 1,810 of them met inclusion criteria. The elderly population was the most affected group, with a mean age of 60 years (Malignant 61 versus Benign 52; p 0.001). There was a trend of female predominance, representing 57% vs 42% of males ( p 0.727). White patients constituted the majority of the population (72%), followed by Black (13%) and Hispanics (10%), with a minority of Native Americans and Asian/ Pacific Islanders ( p 0.016). Medicare was the most frequent primary payer (50%, p 0.015). No difference in household distribution ( p 0.138), hospital teaching status ( p 0.743) hospital region ( p 357) or hospital bed size (0.273) were noted. However, the majority of the admissions were to private-non-profit facilities, accounting for 78% ( p 0.003). Mean LoS was 7.4 days ( p 0.021). On subgroup analysis, the malignant carcinoid tumor of the lung was predominant, with 1,490 malignant carcinoid tumors of the lung and bronchus compared to 329 benign carcinoid tumors of the bronchus and lung. Affection by comorbidities like CAD and COPD was significantly associated with a carcinoid tumor of the lung (17% malignant carcinoid tumor of the lung and bronchus and 5% benign carcinoid tumor of the lung and bronchus p 0.003 and 24% malignant carcinoid tumor of the lung and bronchus and 11% benign carcinoid tumor of the lung and bronchus, p 0.008 respectively). All deaths (n = 90) were observed in the malignant carcinoid lung tumor group. Conclusions: In this cross-sectional study of patients with NET of the bronchus and lung admitted to acute care, we found that patients over the age of 50 and Whites were the most affected, with patients with malignant tumors being older. As expected, Medicare was the most frequent primary payer. In addition, COPD and CAD were not uncommon among both groups.
Deep multi-omic analyses to identify targetable pathways in desmoplastic small round cell tumor (DSRCT) with opportunities for clinical intervention.
Authors: Limin Zhu, Jamie Keck, Jayne Stommel, Brett Johnson, Christopher L. Corless, Christopher W. Ryan, Gordon B. Mills, Lara E. Davis
Journal: Journal of Clinical Oncology (2023)

e22006 Background: DSRCT is an extremely rare and highly aggressive soft-tissue sarcoma affecting adolescents and young adults with male predominance. The 5-year overall survival is &lt; 25% despite intensive multi-modality treatment including aggressive surgical resection, radiotherapy, chemotherapy, and targeted therapy. Therefore, more effective and innovative therapeutic options are urgently needed. Recent advances in genomic, epigenomic, proteomic, and immune profiling have uncovered a large number of therapeutic targets that are transforming the field of cancer medicine. This study aimed to identify novel targetable pathways in DSRCT using a deep multi-omics-based platform. Methods: Three patients with biopsy proven metastatic DSRCT were enrolled under an IRB-approved observational study within the “Serial Measurements of Molecular and Architectural Responses to Therapy” (SMMART) program at OHSU. Biopsies taken at enrollment were analyzed with targeted DNA sequencing, whole transcriptome sequencing, immunohistochemistry (IHC), NanoString GeoMx digital spatial profiling (DSP) multiplexed proteomics, single cell cyclic immunofluorescence (Cyc-IF), and reverse phase protein array (RPPA). Results: Multiple clinically relevant targets were identified, including HER2, androgen receptor (AR), elevated DNA damage response, and MAPK and mTOR signaling pathways. All three DSRCTs expressed HER2: clinical IHC identified HER2 low (1+) to HER2 equivocal (2+) expression; DSP analysis showed high HER2 and phospho-HER2 expression; and HER2 RNA expression was elevated compared to the TCGA sarcoma cohort. Two of the three patients displayed high AR protein expression, assessed by clinical IHC (90-100% positive cells) and DSP (top quartile compared to a 20 mixed-subtype breast cancer cohort). Strong evidence of DNA damage response was demonstrated at both RNA and protein levels, and RPPA revealed high PARP1, PAR, p-ATM, p-RPA32, and RAD51. Within cell signaling pathways, one DSRCT exhibited high total and phospho-ERK1/2 protein across all clinical and exploratory assays, while another patient displayed evidence of elevated mTOR pathway signaling by RPPA. Conclusions: Overall, this multi-omic analysis provided new insights into possible therapeutic targets for this rare and difficult to treat sarcoma subtype. Results from this study will be further validated in vivo using patient-derived xenograft (PDX) models, providing support for development of multiple early phase trials.
Pilot trial of the feasibility, acceptability, and potential efficacy of a pain management intervention adapted for older adults with cancer in rural settings.
Authors: Megan J. Shen, Tammy Stokes, Sarah Yarborough, Jill Harrison
Journal: Journal of Clinical Oncology (2023)

e24021 Background: Among the growing older adult U.S. population, under-treated cancer pain is a major public health concern. Those living in rural areas are even more vulnerable due to less access to care, patients’ concerns around the over-use of pain medication, and patients’ preferences for non-pharmacological interventions. There is a clear need for interventions designed to improve pain management among this vulnerable population. Methods: In this study, older adults with cancer (age 65+ years) were enrolled in an open arm trial in rural Tennessee to test feasibility, acceptability, and potential efficacy of a previously developed intervention, Ca-HELP, to improve pain communication with one’s oncologist. Prior to the trial, the original Ca-HELP intervention was adapted for use among older adults in rural settings. Feasibility was examined through accrual and intervention completion rates. Acceptability was measured through single-item questions assessing helpfulness, difficulty, and satisfaction with the intervention. Intervention efficacy was assessed using mean score differences from pre- and post-intervention assessments of pain self-management, self-efficacy for communicating with physicians about pain severity, pain severity, and misconceptions about pain. Mean score differences were analyzed using one-tailed paired samples t-tests, with an alpha level = 0.05. Results: A total of n = 30 patients were enrolled in this trial, adequately powering this trial (0.85) to detect moderate effect size differences. Participants were 56.7% female, predominately white (80.0%), less educated (53.3% less than high school), and lower income (50.0% household income less than $21,000). Fidelity rates of 90% for communication consistency (pacing, volume, introduction to purpose of intervention) and 100% for delivery of intervention components were observed. This intervention was highly feasible, with a 100% accrual rate and 100% intervention completion rate. Regarding acceptability, all patients (n = 30) rated the intervention as helpful, with the majority rating it as “very helpful” (n = 24, 80.0%). Most patients rated the intervention as “not at all difficult” (90.0%), enjoyed participating in the intervention (70.0%), and were “very satisfied” with the intervention (83.3%). Pre/post changes in outcomes indicated significant improvements in pain self-management and self-efficacy for communicating with physicians about pain severity, as well as significant reductions in pain severity and pain misconceptions (all p &lt; .05). Conclusions: Results of this study indicate the adapted version of Ca-HELP was feasible, acceptable, and had potential efficacy for improving pain related outcome measures among older adults with cancer in a rural setting. Clinical trial information: NCT04262232 .